PROJECT SUMMARY (from Parent R00 ? project summary is not beingchanged by the proposed supplement activities) Associations between heightened maternal psychological stress during pregnancy and increased risk of offspring psychopathology have been demonstrated repeatedly. Evidence points to the integral role of limbic- prefrontal brain systems (LPFS) in mental health outcomes, and the vulnerability of LPFS to early life stress. Early development of LPFS is therefore an important potential target for preventive interventions aimed at supporting healthy brain development and preventing mental health disorders. The current proposal is designed to advance understanding in this area in several ways. First, the study takes advantage of methodological advances, which allow for examining brain functioning in newborn infants, increasing capacity to isolate pre- from postnatal influences and thereby clarify the role of maternal psychological stress during pregnancy in the development of LPFS. Second, the proposed research employs repeated measurement of maternal psychological stress to allow for examining different aspects of stress, including intensity, variability and timing, in relation to infant LPFS. Finally, the framework for understanding associations between maternal psychological stress during pregnancy and offspring brain systems remains correlational. This proposal seeks to advance causal understanding regarding the influence of maternal psychological stress on offspring LPFS by employing an intervention designed to reduce maternal psychological stress during pregnancy. The study will focus on a sample of pregnant women enriched for heightened levels of psychological stress (N=120). It will employ a randomized-controlled-trial of an established stress reduction intervention, which has been tailored for pregnant women, Mindfulness-Based Cognitive Therapy (MBCT). Psychological stress will be assessed repeatedly throughout pregnancy and newborn LPFS will be examined with structural and functional magnetic resonance imaging in the neonatal period. The study will examine effects of MBCT on maternal psychological stress during pregnancy, including potential alterations in the overall magnitude and trajectory of stress. Additionally, the potential for MBCT during pregnancy to impact newborn LPFS will be examined. Finally, this work will test the full hypothesis that intervention-induced reduction in maternal psychological stress will influence newborn LPFS with implications for subsequent development of negative affect and risk for mental health disorders. Establishing the capacity to impact maternal psychological stress during pregnancy and newborn LPFS has practical implications for supporting healthy brain development and preventing psychiatric disorders. Importantly, intervention research also has the benefit of creating an experimental design which can advance the field beyond examining correlational associations between maternal psychological stress and offspring development, and towards understanding a causal role for maternal psychological stress during pregnancy in the intergenerational transmission of risk for mental health disorders.